1. Field of the Invention:
This invention relates to a permeable membrane and a method for the manufacture thereof. Particularly, this invention relates to a permeable membrane useful as for filtration of blood plasma and a method for the manufacture of the permeable membrane. To be more particular, this invention relates to a permeable membrane possessed of pores of a controlled diameter and enabled to provide efficient removal of pathogenic macromolecules, ensure recovery of albumin in a high ratio and permit efficient treatment of a large amount of blood plasma and to a method for the manufacture of the permeable membrane.
2. Description of Prior Art:
Heretofore, various permeable membranes have been used for the separation of whole blood into blood corpuscles and blood plasma. For example, the permeable membrane for the separation of blood plasma is used for the preparation of a blood plasma medicament for transfusion, for the pretreatment of an artificial kidney, and for the therapy resorting to change of blood plasma. The therapy by the change of blood plasma has been demonstrated to be effective against such auto-immunizing diseases as hepatic insufficiency, serious myasthenia, and chronic arthrorheumatism. This therapy is effectively carried out by separating the whole blood from the patient into blood corpuscles and blood plasma, then discarding the blood plasma containing a pathogenic substance, and adding to the blood corpuscles the blood plasma taken from a healthy man or a blood plasma medicament. The use of the blood plasma medicament entails such problems as the difficulty in the procurement of the medicament itself and the possibility of evil effect of infections factor. Thus, the method which comprises clarifying the blood plasma separated from the patient's own whole blood and recombining the clarified blood plasma with the blood corpuscles also separated from the whole blood proves desirable. The desirability of developing a membrane effective for the purpose of this separation is urged.
As membranes useful for such separation of blood plasma as described above, regenerated cellulose membrane, cellulose acetate membrane, polyvinyl alcohol membrane, polysulfone membrane, polymethyl methacrylate membrane, etc. have been known to the art. These high molecular membranes are deficient in mechanical strength, pore diameter of membrane, capacity for treatment of blood plasma, etc. Most of them are impervious to albumin which is beneficial to the human system, pervious not only to albumin but also to pathogenic macromolecules, or susceptible of early clogging and, therefore, incapable of removing pathogenic macromolecules in a sufficient amount. The term "pathogenic macromolecule" as used herein means immune globulin M (IgM, Mw about 950,000), low density ripoprotein (LDL, Mw about 1,200,000 to 3,300,000), immune complexes, rheumatic factor, etc. which have larger molecular weights than albumin. For the purpose of removing pathogenic macromolecules aimed at and returning albumin as a beneficial blood plasma component to the patient's system, it is necessary to use a separation membrane which possesses desired pore diameter and porosity and a membranous texture difficult to clog, and permits clarification of a large amount of blood plasma.
As a separation membrane for the removal of blood plasma components of medium to high molecular weights, there has been proposed a porous polyethylene hollow-fiber membrane which is made of high-density polyethylene having a density of at least 0.955 g/cm.sup.3, possessed of a multiplicity of fine pores penetrating the wall thereof from the inner wall surface through the outer wall surface of the hollow fiber, oriented in the direction of length of the hollow fiber, and possessed of a porosity in the range of 30 to 90% by volume (Japanese Patent Laid-open SHO No. 58(1983)-75,555). In the hollow fiber membrane described above, since the fine pores are mechanically formed by cold drawing a high-orientation blood plasma type unstretched hollow fiber and subsequently hot drawing the cold drawn hollow fiber and, moreover, the fine pores so formed are substantially straight and substantially uniform in diameter from the inner wall surface through the outer wall surface, the pore density per unit volume cannot be increased and the capacity for blood plasma treatment per unit surface area is small and the ratio of recovery of albumin is low. Further, the membrane is readily fractured by orientation and is heavily deformed and shrunken by the intense heat as generated during the sterilization with an autoclave, for example.
A hollow fiber made of a vinyl alcohol type polymer and possessed of a compacted layer on at least one of the opposite surfaces of the hollow fiber membrane and a porous layer in the interior of the web of the hollow fiber membrane has been proposed (U.S. Pat. No. 4,402,940). Since the hollow fiber membrane of this type is obtained by spinning the solution of the vinyl alcohol type polymer, however, it suffers from the disadvantage that the pore density per unit volume cannot be increased, the capacity for blood plasma treatment per unit volume is small, the pathogenic macromolecules cannot be sufficiently removed, and the ratio of recovery of albumin, etc. is low.
There has been proposed a permeable membrane which is produced by preparing a mixture of a polymer such as crystalline polyolefin or polyamide which is sparingly soluble in a solvent and is stretchable with a compound which is partially compatible with the polymer and is readily soluble in a solvent, molding the mixture in the form of film, sheet, or hollow member, treating the molded mixture with a solvent, drying the wet molded mixture, and stretching the dried molded mixture monoaxially or biaxially at an elongation of 50 to 1,500% (U.S. Pat. No. 4,100,238). Since this membrane is stretched exclusively for the purpose of enlarging the pores in diameter, it exhibits low mechanical strength and poor durability. Further since the pores are substantially uniform in structure in the opposite surfaces and in the interior and the polymer crystals are coarse, it separates the components of medium to high molecular weights with difficulty despite its low strength.
It is, therefore, an object of this invention to provide a novel permeable membrane and a method for the manufacture of this permeable membrane.
Another object of this invention is to provide a permeable membrane useful as for filtration of crystals and a method for the manufacture of the permeable membrane.
Still another object of this invention is to provide a permeable membrane possessed of pores of a controlled diameter and enabled to recover albumin in a high ratio, remove pathogenic macromolecules with high efficiency, and treat a large amount of blood plasma and a method for the manufacture of the permeable membrane.
Yet another object of this invention is to provide a porous membrane useful for separating blood components having good heat stability without any change in membrane structure and permeability by thermal history and a method for the manufacture thereof.
Still yet another object of this invention is to provide a porous membrane capable of giving sufficient permeability without further stretching and a method for the manufacture thereof.